TY  - CHAP
M1  - Book, Section
TI  - Myeloma
A1  - O’Donnell, Elizabeth
A1  - Cottini, Francesca
A1  - Raje, Noopur
A1  - Anderson, Kenneth
A2  - Press, Oliver W.
A2  - Lichtman, Marshall A.
A2  - Leonard, John P.
Y1  - 2017
N1  - 
T2  - Williams Hematology Malignant Lymphoid Diseases
AB  - SUMMARYMyeloma  derives  from  the  proliferation  of  a  clone  of  malignant  plasma  cells  that  secretes  a  complete  and/or  partial  monoclonal  immunoglobulin  protein.  It  originates  in  most,  perhaps  all,  cases  from  an  antecedent  monoclonal  gammopathy  (essential  monoclonal  gammopathy)  that  progresses  by  clonal  evolution  (acquisition  of  additional  mutations)  to  a  malignant  B-cell  malignancy,  often  myeloma,  at  a  rate  of  1  percent  per  year.  Myeloma  cells  accumulate  in  the  marrow  microenvironment,  where  contact  with  extracellular  matrix  and  interaction  with  marrow  accessory  cells,  such  as  osteoblasts,  osteoclasts,  and  stromal  cells,  evokes  cell  growth  and  cell-survival  signals  and  contributes  to  resistance  to  therapy.  Myeloma  cells  show  a  complex  genomic  phenotype,  with  chromosomal  translocations  and  small  copy  number  variations  that  affect  patient  prognosis.  Patients  with  myeloma  have  signs  resulting  from  marrow  infiltration  (anemia),  bone  destruction  (bone  pain,  pathologic  fractures),  excessive  immunoglobulin  production  and  deposition  (renal  failure  and  amyloidosis-related  symptoms),  and  immunosuppression  (e.g.,  infection).  Clinical  manifestations  of  myeloma  vary  as  a  result  of  the  heterogeneous  biology,  spanning  the  entire  spectrum  from  indolent  to  highly  aggressive  disease  with  extramedullary  features.  Diagnostic  workup  of  myeloma  should  include  serum  protein  electrophoresis  together  with  immunoglobulin  immunofixation;  serum-free  light-chain  assay;  a  24-hour  urine  collection  to  quantitate  urinary  protein;  basic  blood  metabolic  panel,  including  blood  counts  and  renal  function;  and  marrow  aspirate  or  biopsy  with  fluorescence  in  situ  hybridization  and  cytogenetic  studies.  Radiographic  bone  survey  is  used  to  detect  osteopenia  and  bone  lesions  or  impending  fractures.  Magnetic  resonance  imaging  (MRI)  is  more  sensitive  than  the  bone  survey,  can  identify  early  bone  disease  and  extramedullary  disease,  and  can  distinguish  myeloma  from  normal  marrow,  helping  in  quantifying  the  extent  of  the  disease.  Positron  emission  tomography  coupled  with  computed  tomography  (PET-CT)  detects  metabolically  active  intramedullary  or  extramedullary  myeloma  foci  and  lytic  bone  lesions.  The  most  common  staging  system  for  myeloma  is  the  International  Staging  System,  based  on  two  parameters,  serum  β2-microglobulin  (β2M)  and  albumin;  three  stages  are  defined  and  correlate  with  patient  outcome.  Serum  levels  of  β2M,  C-reactive  protein,  and  number  of  circulating  plasma  cells  and  their  labeling  index  are  related  to  patient  prognosis.  Other  prognostic  factors  include  the  presence  of  specific  chromosomal  abnormalities  (deletion  of  chromosome  17p  and  loss  of  chromosome  1p/gain  of  chromosome  1q),  altered  gene-expression  profiling,  as  well  as  MRI  and  PET-CT  abnormalities.  The  introduction  of  the  immunomodulatory  drugs  (IMiDs)  thalidomide  and  lenalidomide  and  the  proteasome  inhibitor  bortezomib  have  increased  the  5-year  relative  survival  rate  to  45  percent,  with  some  patients  achieving  long-term  survival  of  more  than  10  years.  Melphalan-based  autologous  hematopoietic  stem  cell  transplantation  in  combination  with  novel  agents  can  achieve  remarkable  results  in  patients  with  good-risk  myeloma;  patients  who  are  not  eligible  for  autologous  transplant  have  traditionally  been  treated  with  melphalan  and  prednisone;  novel  agents  such  as  bortezomib  and  lenalidomide  are  also  active  and  well  tolerated  in  this  population.  Consolidation  and  maintenance  regimens  based  on  lenalidomide  as  a  single  agent  or  in  combination  with  bortezomib  have  been  evaluated  to  extend  the  duration  of  complete  remission  following  autologous  stem  cell  transplant.  Finally,  several  novel  agents  can  be  used  in  the  setting  of  relapsed/refractory  disease,  including  ...
SN  - 
PB  - McGraw-Hill Education
CY  - New York, NY
Y2  - 2024/04/16
UR  - hemonc.mhmedical.com/content.aspx?aid=1148369608
ER  -